Molecules in blood, urine may help detect PH in children with CHD
5-HIAA and IGF-1 show potential as 'reliable' biomarkers in study in babies
Two molecules, 5-hydroxyindoleacetic acid (5-HIAA) and insulin-like growth factor 1 (IGF-1), showed a potential to diagnose pulmonary hypertension early in children with congenital heart disease based on their levels in blood and urine samples examined in a study.
5-HIAA is the main product of the breakdown of serotonin, a signaling molecule that regulates vascular tone — the degree of blood vessel constriction — while IGF-1 is reported to influence blood vessel widening and heart muscle cell survival.
“Our research highlights the significant roles of the serotonin system and IGF-1 in the development of pediatric pulmonary hypertension (PH). Our data show strong links between these substances and PH, suggesting their potential as biomarkers for diagnosis and prediction,” the researchers wrote.
The study, “Identifying Key Biomarkers in Pediatric Pulmonary Hypertension: An Investigative Approach,” was published in the journal MDPI.
Diagnosing pulmonary hypertension in young children can be difficult
PH is characterized by high blood pressure in the pulmonary arteries, the blood vessels that supply the lungs. As a result, the heart’s right ventricle needs to work harder to pump blood through the lungs and becomes progressively enlarged and weakened.
The disease also a common complication of congenital heart disease (CHD) — birth defects that impair the heart’s function. Early PH detection and treatment can significantly improve outcomes and reduce the risk of complications, but diagnosing PH can be particularly challenging in young children.
“Biomarkers reflecting changes in the structure and function of pulmonary vessels, endothelial dysfunction and remodeling processes in the heart muscle” are needed, the researchers, all in Kazakhstan, wrote. The endothelium is the cell layer lining the interior of blood vessels; remodeling refers to changes in blood vessel structure and arrangement.
Scientists analyzed the potential of 5-HIAA and IGF-1 — measured in the blood and urine — to be biomarkers for the diagnosis, monitoring, and prognosis of PH complicated by CHD. Samples were collected from 46 infants with PH and CHD, with a median age of 8.5 weeks, and 24 healthy babies (median of 8 weeks old) who served as controls.
Plasma (liquid component of blood), platelets (cell fragments that form clots to stop bleeding), and urine levels of 5-HIAA and IGF-1 in both groups were analyzed.
5-HIAA levels were significantly lower in patients’ plasma but higher in their urine relative to controls, the researchers reported. No differences were found between the two groups in platelets.
The platelets-to-plasma ratio of 5-HIAA was significantly higher in patients, whereas the 5-HIAA ratio between plasma and urine was “even more significantly reduced,” they added.
‘Potential disruptions in serotonin and IGF-1 metabolism in PH patients’ noted
To determine the diagnostic relevance of 5-HIAA, the researchers calculated its area under the receiver operating characteristic curve (AUC), used to determine how well a measure can differentiate between two groups. Higher values indicate a better ability to differentiate.
Specifically, they determined the AUC of 5-HIAA based on creatinine urine levels, with a cutoff value of 3 nanograms (ng)/moles of creatinine for distinguishing between patients and controls. Creatinine is a waste product from the digestion of protein and the normal breakdown of muscle tissue.
In these samples, the AUC for 5-HIAA was 0.871 with strong specificity (79.3%; the test’s ability to correctly identify an individual with PH) and sensitivity (80%; its ability to correctly identify an individual without PH). This indicated high test accuracy, the scientists noted.
Neither platelet-to-plasma or plasma-to-urine ratios for 5-HIAA were superior to urine levels at detecting PH.
Both plasma levels of IGF-1 and its plasma-to-platelet ratio were significantly reduced in children with PH and CHD.
“Our data also revealed altered indices reflecting the equilibrium between plasma and platelet 5-HIAA and IGF-1, highlighting potential disruptions in serotonin and IGF-1 metabolism in PH patients,” the researchers wrote.
The IGF-1 plasma/platelet ratio had an AUC of 0.929, with high specificity (85.7%) and sensitivity (95%). In addition, its positive predictive value (the percentage of patients diagnosed with PH after screening positive) and negative predictive value (those not diagnosed with PH after a negative test) were both high.
“This makes it a reliable diagnostic tool,” the investigators wrote.
“5-HIAA and IGF-1 levels correlate well with PH, underscoring their diagnostic value for early PH detection in children with CHD,” the researchers concluded. However, “further studies on larger patient populations are needed to confirm these roles and investigate their interactions with other molecules.”
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